Synthesis and structure guided evaluation of estrogen agonist and antagonist activities of some new tetrazolyl indole derivatives.

Several regioisomeric tetrazolyl indole derivatives with structurally modified alkyl substituents at the tetracyclic indole nitrogen containing N-ethyl amino tetrazole moiety have been synthesized and screened for their ER binding affinity, agonist (estrogenic), antagonist (antiestrogenic) and anti-implantation activities. N-2 regioisomers were found to be moderately antagonists and one compound showed 100% contraceptive efficacy at 10 mg/kg dose. Molecular docking studies carried out in comparison to estradiol and raloxifene showed different binding modes of the two regioisomers to the binding site.

Once weekly thyroxine treatment as a strategy to treat non-compliance.

Hypothyroidism is a common disorder, which is mainly treated in primary rather than secondary care. Once daily thyroxine replacement restores euthyroidism in most patients; some patients, however, remain hypothyroid despite adequate thyroxine replacement. Non-compliance is the most common cause of lack of response to thyroxine treatment. We describe two cases of primary hypothyroidism in which daily thyroxine treatment did not restore biochemical euthyroidism but once weekly thyroxine treatment was successful. In addition we review the evidence and discuss the differential diagnosis of lack of response to thyroxine treatment. Once weekly thyroxine treatment can be a safe, well-tolerated, and effective therapy for patients with non-compliance.

Grave's Eye disease developing following radioiodine treatment for toxic nodular goitre.

The development of Grave's ophthalmopathy (GO) following radioiodine (RI) treatment for Grave's thyrotoxicosis, though controversial, is well described. The development of ophthalmopathy following RI treatment for toxic nodular goitre is much less recognised. We report a 49 year-old female patient who developed thyrotoxicosis and GO after receiving RI treatment for toxic nodular goitre and we also review the relevant literature.

Evaluation of glargine group-start sessions in patients with type 2 diabetes as a strategy to deliver the service.

Improving glycaemic control in patients with type 2 diabetes reduces microvascular complications. The national service framework for diabetes and the new general medical service contract have been aiming to direct more focus on improving HbA1c. These measures have resulted in increasing number of patients being initiated on insulin therapy, which increases the workload of diabetes specialist nurses (DSNs). Initiating insulin on a one-to-one basis is time consuming. As a result DSN-led insulin group-start sessions were introduced. To evaluate DSN-led glargine group-start and self-titration as a strategy of providing service. We assessed the impact of this method on the use of DSNs time, HbA1c and on patients' satisfaction. A prospective audit in a district general hospital. Groups of 5-7 patients received two 2-h sessions at weeks 0 and 2. During these sessions, patients were initiated on insulin glargine and received an educational package and a self-titration protocol. DSNs did not see patients after week 2. Patients were able to phone the DSNs for advice till the end of the titration period. Patients completed Diabetes Treatment Satisfaction Questionnaire (DTSQ) at baseline, week 2 and 12 months. Weight and HbA1c were assessed at base line and 12 months later. Twenty-nine consecutive patients were included. Baseline HbA1c improved at 6 months and remained stable at 12 months (medians 10.0, 8.7 and 8.9 respectively, p < 0.001). DTSQ score improved between week 0 and 2 and this was maintained at 12 months (medians 26, 35 and 34 respectively, p < 0.001). After week 2, the DSNs spent a median of 21 min advising patients by phone during the titration period. Weight did not increase significantly. In our centre, DSN-led insulin group-start sessions and self-titration improved glycaemic control. Patients were satisfied with this method of starting insulin. This was achieved with minimal DSNs time and input and proved to be effective, yet less time consuming.

Steroid responsiveness in a case of Riedel's thyroiditis and retroperitoneal fibrosis.

Riedel's thyroiditis is a rare chronic inflammatory disease of the thyroid characterised by an invasive fibrotic process. We present a lady with newly diagnosed hypothyroidism, rapidly enlarging hard, fixed goitre, strongly positive thyroid antibodies and raised erythrocyte sedimentation rate (ESR). A tru-cut biopsy confirmed Riedel's struma. Regression of the goitre and reduction of antibody titres occurred after starting prednisolone, which was stopped after 10 months. Six months later, she presented with renal failure due to retroperitoneal fibrosis that was successfully treated by reinstitution of steroids and ureteric stenting. Very high titres of thyroid antibodies and hypothyroidism predating development of goitre suggest coexistence of Hashimoto's thyroiditis and Riedel's thyroiditis. Tru-cut biopsy obviated the need for open thyroidectomy. A predominantly inflammatory as opposed to fibrotic thyroid histology may predict good response to steroids. Relapse following steroid withdrawal may not only be in the thyroid but also at other sites.

Phaeochromocytoma presenting as dilated cardiomyopathy.

Phaeochromocytomas are rare endocrine tumours that secrete excessive amounts of catecholamines and can lead to myocarditis and cardiomyopathy. We report a 63-year-old man with long-standing hypertension and diabetes who presented with dilated cardiomyopathy, which was initially thought to be secondary to ischaemic heart disease. Subsequent coronary angiography was normal. Carvedilol therapy unmasked the characteristic features of phaeochromocytoma. Surgical resection of a right adrenal tumour cured his symptoms, hypertension and diabetes, as well as causing a substantial improvement in cardiac function. Phaeochromocytoma should be considered as a rare cause of dilated cardiomyopathy of uncertain aetiology.

Non-linear material models for tracheal smooth muscle tissue.

The aim of this study is to investigate the hyperelastic material models to describe the non-linear stress-strain behavior of tracheal smooth muscle tissue. Specifically, the goal is to validate the material model with experimental data using different finite element models and discuss the trends in stress-strain behavior of smooth muscle tissue. Both 2D and 3D finite element analyses were carried out to estimate the stress-strain behavior of the smooth muscle tissue. The results obtained indicate that the developed Ogden material model is valid and useful in explaining the stress strain behavior of tracheal smooth muscle tissue under different conditions. Finite element simulation results of the stress-strain behavior in the transverse direction are presented.

Successful resuscitation of a patient with electrical storm.

A 41 year old woman with type 2 diabetes, hypertension, and hyperlipidaemia but no known heart disease received 130 DC shocks for repeated cardiac arrests due to ventricular tachyarrhythmias over 48 hours. She was stabilised by intravenous amiodarone and had a defibrillator implanted. Serial ECGs did not change, but raised troponin I confirmed myocardial infarction as the underlying cause. Electrical storm is an uncommon and dramatic but usually treatable syndrome of recurrent ventricular arrhythmias. Frequent precipitants of electrical storm include recent worsening heart failure, hypokalaemia, hypomagnesaemia and myocardial ischaemia. Amiodarone is the antiarrhythmic agent of choice and implantable cardioverter defibrillator improves long term outcome.

Hypertension, anti-hypertensive drug therapy and erectile dysfunction in diabetes.

AIMS: Erectile dysfunction (ED) is common in diabetes and may be related to the high prevalence of hypertension and consequent anti-hypertensive drug therapy in diabetic patients. The risk factors for ED were studied with particular reference to hypertension and anti-hypertensive drugs. METHODS: We performed a retrospective case note analysis of 763 consecutive male patients (34% Type 1 diabetes, 65% Type 2 diabetes) attending an adult diabetic clinic to collect data on risk factors for ED. We specifically recorded the use of anti-hypertensive drugs. RESULTS: Two hundred and ninety-nine (39%) patients had ED. Mean age of patients with ED (61 years) was higher than those without (mean age 51 years, P < 0.001). The mean age of hypertensive patients was also significantly higher than those without. On multivariate regression analysis, age (P < 0.001), macrovascular disease (P < 0.001), sensorimotor neuropathy (P < 0.001) and HbA1c (P < 0.05) predicted ED. Neither hypertension nor any anti-hypertensive medication independently predicted ED. CONCLUSION: Our data suggest that ED in diabetic patients with hypertension may be related to the higher age and prevalence of macrovascular disease rather than hypertension or its treatment.

The role of somatostatin receptor scintigraphy in the management of pituitary tumours.

The detection of functioning neuroendocrine tissue bearing somatostatin receptors has been facilitated to a large extent by the availability of radiolabelled octreotide scanning with 111In octreotide. This review discusses the possible role for somatostatin receptor scintigraphy (SRS) in the evaluation of pituitary adenomas.